Process stations/production units which are used in the production and processing of pharmaceutical active ingredients, pharmaceutical galenical forms, biotechnologically produced active ingredients, foods, etc., and systems and units which are used in the production and distribution of these products, as well as systems and units which are operated with ultrapure water, purified water and ultrapure vapor, are usually made from stainless steels based on stainless steel alloys. Examples include: Mixing vats, recipient vessels, storage containers, fermenters, dryers, filling machines, autoclaves, sterilization vessels, freeze dryers, washing machines, CIP units, ultrapure water generators, ultrapure vapor generators, distribution lines for the media (purified water, ultrapure water, ultrapure vapor, products) etc.
Despite the use of high quality materials such as e.g. stainless steels (e.g. CrNiMo steels of grades AISI 316L, AISI316Ti, or AISI 904L), after a while, discolorations can usually be observed on the surfaces that come in contact with the media, which are also known as “rouging” in the pharmaceutical industry, and characteristic brown-red particles are carried to the final product or the final stage of the production unit.
A wide variety of surface changes can occur on stainless metallic surfaces. They are often precipitates of iron oxides which occur in the form of fine reddish-brown iron oxide or iron hydroxide particles and usually comprise Cr, Ni and Mo components. These particles are usually of a powdery consistency and therefore only adhere loosely to the surface. They can therefore easily wiped off mechanically, but often leave a visible discoloration of the metallic surface. Other manifestations of these surface changes occur in the form of adhering films or deposits which can no longer be removed mechanically but have to be subjected to a chemical treatment. These newly formed surface layers can exhibit a color spectrum of yellow, blue, red, brown and black.
In particular in the pharmaceutical and food processing industries, the occurrence of these surface changes holds the danger of undesired contamination with heavy metal particles that flake off and are distributed into other systems and thus negatively affect the purity and quality of the production and processing products.
Depending on the operating intensity and conditions, these surface changes can occur as early as a few months after a unit is first started up. In other cases, it may be years until such changes are first observed.
As far as the formation of the surface change known as “rouging” is concerned, there is at this point no hard scientific data. According to the prevailing opinion among experts at present, the rouging phenomenon is a selective destruction of the chromium oxide-rich passive layer in the stainless steel surface in contact with the media due to the formation of an iron oxide-rich corrosion layer, with an additional effect being the formation and distribution of corrosion particles in the system.
Said rouging is therefore characterized by the occurrence of a typical iron oxide or iron hydroxide layer on the surface of the stainless steel material wherein these typical haematite or magnetite layers comprise intercalated Cr, Ni and Mo which indicates a tendency of the stainless steel material to dissolve layer by layer. As a rule, the rouging layers have a thickness of 0.1 to 10 μm whereby only the thinner films are to be considered rouge contamination; more massive films, on the other hand, would more likely be rust contamination.
It has been shown that the changes described above increasingly appear in systems which are operated with ultrapure water, or media-conducting ultrapure water, or with ultrapure (water) vapor, with elevated temperatures apparently accelerating the process of surface changing. The formation of surface changes is also influenced by the atmospheric conditions prevalent in the various systems, the various media conditions (e.g. pH<7), the quality of the material (composition of the alloy) and the surface finish. Depending on the operating time and conditions, films/deposits of different thicknesses are foamed.
Apparently, what triggers the formation of rouge is a local depassivation of the chromium oxide protective layer of the stainless steel surfaces caused by the parameters mentioned above, triggered by the breakdown of said protective layer at discrete surface points as well as the lack of a sufficient amount of oxygen for repassivation.
This mechanism of local depassivation is promoted by the considerably reduced amount of dissolved oxygen in hot waters (WFI>70° C. or steam) as well as by a strongly increased capacity for ion dissolution due to the purity of said waters.
The elevated temperatures inter alia cause iron atoms to increasingly diffuse to the surface and to react with the oxygen present at the surface to form oxides and hydroxides.
In order to allow a trouble-free reconstruction of the chromium oxide-free passive layer and to reduce the risk of a carry-over of detaching heavy metal particles and the risk of contamination of the products manufactured at the process stations and production units, it is necessary to completely remove and dispose of the rouging and rouging contamination layers rich in iron oxide while at the same time taking care of the stainless steel surfaces.
These films/deposits therefore have to be removed periodically using mechanical or wet-chemical cleaning processes or combinations thereof.
Mechanical cleaning processes during which the particles adhering loosely to the surface are removed e.g. by wiping with a cloth are usually limited to easily accessible areas. Such processes are not suitable to remove more permanent discolorations as well adhering films and deposits.
Wet-chemical cleaning processes aim at chemically removing the films/deposits. For this purpose, cleaning solutions containing inorganic acids are used almost exclusively.
So far, cleaning processes based on neutral cleaning solutions, as they were occasionally suggested for the removal of rust deposits on pipe systems conducting cold or hot water and containers made from black steels, have not been considered for the removal of rouging on media-contacted stainless steel surfaces.
Such neutral cleaning solutions are e.g. described in U.S. Pat. No. 6,310,024, U.S. Pat. No. 5,587,142, U.S. Pat. No. 4,789,406 for cleaning boilers, instant water heaters, and the like, for the removal of rust and/or lime deposits.
EP 1 621 521 and EP 1 300 368 disclose the use of neutral cleaning agents for the removal of deposits from systems conducting cold water, in particular water supply equipment such as e.g. drinking water containers.
Rouging on media-contacted stainless steel surfaces of process stations and production units operated with ultrapure water has a different quality than the rust and lime deposits described in the above-mentioned prior art which are formed on surfaces made from black steels or non-metallic surfaces. In practical applications, the complete removal of rouging on stainless steel surfaces has been found to be extremely costly and difficult, which led to the conventional wisdom that the use of strong and highly concentrated mineral acids is absolutely necessary despite the numerous known disadvantages.
When handled improperly, the use of concentrated mineral acids can sometimes entail considerable danger, both with respect to its transport and to its use as a component of the cleaning solution itself. In addition to the corrosive and strongly caustic effect of an acid such as concentrated hydrochloric acid, sulfuric acid or phosphoric acid, its vapors can cause severe respiratory irritations as well.
Organic acids, e.g. oxalic acid and/or citric acid, are sometimes used for cleaning off films/deposits as well. However, organic acids do not possess the same solubilizing capacity as highly concentrated mineral acids so that often mixtures of organic and inorganic acids are used too. Sometimes, complexing agents, e.g. EDTA or NTA, are added to these acid mixtures. One major disadvantage of such acid mixtures lies in the fact that they do not specifically remove the films/deposits in the form of oxidic iron compounds, but also partly dissolve the heavy metals additionally present in the alloy of the stainless steel. Thus, when handled improperly, there is the danger that the surface of the process stations and production units is attacked and the surface properties are negatively affected. Moreover, these cleaning solutions usually have a high heavy metal content after use so that the solutions subsequently have to be disposed of in a costly and professional manner.
In order to compensate for these disadvantages, specific additives were added to the cleaning solutions used for rouging contamination in practical applications in order to alleviate the negative effects the concentrated mineral acids have on the stainless steel surfaces, and complex process management and control protocols were drawn up in order to ensure a minimal dwell time of the cleaning solution on the stainless steel surface in combination with a maximum cleaning effect, as it is e.g. described in the “Technical Bulletin” of the company Henkel (Essay No. 26/Rev, 00, 2003).